Beta-tricalcium Phosphate Research Articles

Fabrication and properties of βTCP/Zeolite/Gelatin scaffold as developed scaffold in bone regeneration: in vitro and in vivo studies

Synthetic scaffolds, as an alternative to allograft and xenograft scaffolds, are suitable for bone regeneration. This study aimed to synthesize a composite biomaterial of zeolite and beta-tricalcium phosphate (βTCP) to obtain a biocompatible material with physical and mechanical properties in bone regeneration. One scaffold without zeolite (βZG 0) and two scaffolds with different amounts of zeolite (βZG 1 and βZG 2) were synthesized. The scaffolds were evaluated by FTIR, XRD, compressive strength test, MTT assay, and radiographic and histological analyses. The XRD results confirmed the presence of βTCP and ZSM-5 phases in the composite scaffolds and also, indicated that the addition of gelatin decrease the crystallinity of composite scaffolds. FTIR revealed the gelatin, β-TCP and ZSM-5 functional groups in the composite structure. βZG 2 group had the maximum porosity among the scaffolds (74%) ranging in size from 61-600 µm. Compressive strength test showed that the Young’s modulus changed from 23 MPa to 59 MPa, and the zeolite nanostructure was the most influential factor responsible for this change. The MTT assay showed the superiority of βZG 2, and the macroscopic and microscopic results at 4, 8, and 12 weeks revealed the maximum bone regeneration and formation of bone trabeculae in the βZG 2 and βZG 1 groups, respectively. The zeolite scaffold showed the superior mechanical, radiographic and histological properties compared with the control and non-zeolite scaffold. βTCP/ Zeolite/ Gelatin scaffold can be an appropriate candidate for medical application in bone regeneration.

Early Outcomes of an Anterior Ankle Fusion Plating System with rhPDGF-BB Beta Tricalcium Phosphate Graft

Category:Ankle; Ankle ArthritisIntroduction/Purpose:Ankle fusion offers a reliable and effective treatment for end-stage ankle arthritis. Biomechanical studies have shown that plating systems may offer an advantage to ankle fusion patients with significant bone loss, bone deformity, or osteoporotic bone by providing a stiffer construct. One potential downside to plating systems is that they have been associated with soft tissue irritation due to their profile height. The objective of this case series was to assess the early patient clinical and radiographic outcomes of an anatomically designed, lower profile anterior ankle fusion plate used in combination with an autograft alternative, recombinant human protein derived growth factor (rhPDGF-BB).Methods:All ankle fusions performed between May 2018 and August 2019 at two centers were retrospectively evaluated. All patients received an anatomically designed, low profile anterior ankle fusion plate (ORTHOLOC 3Di, Wright Medical Group, Memphis, Tennessee, USA) through an anterior surgical approach. All patients also received rhPDGF-BB as part of the surgical procedure. Patients were non-weight bearing for 6 to 8 weeks in a splint or short leg cast, before transitioning to protected partial weight bearing for another 6 to 8 weeks. Patient demographics, time to radiographic fusion, length of follow-up, and adverse events were collected as part of the review.Results:There were 20 patients (12 male, 8 female) included in the analysis. The average age was 60.9 years (range, 42-90) and the average BMI was 31.6 kg/m2 (range, 21-52). There were eight diabetics, four smokers, and two patients who had preoperative ulcers. The average follow-up time was 7.8 months (range, 3-18). The fusion rate was 90%, with two nonunions. One nonunion patient was an obese, diabetic, neuropathic, smoker with a preoperative ulcer and a previous ankle fracture. She was treated with a bone stimulator and showed increased bony consolidation. The second nonunion patient was a neuropathic, diabetic who had previous hindfoot Charcot reconstruction. Her nonunion was stable and fibrous, which allowed her to ambulate pain free without bracing or assistive devices.Conclusion:This case series presents the first clinical results for this anatomically designed anterior ankle fusion plate. Outcomes were positive with a 90% fusion rate despite being used in a series of patients with a high incidence of risk factors and comorbidities. Additional complications were minor as related to wound healing. Further study is needed to confirm these promising initial results.

Three-Dimensionally-Printed Bioactive Ceramic Scaffolds: Construct Effects on Bone Regeneration.

The utilization of three-dimensionally (3D)-printed bioceramic scaffolds composed of beta-tricalcium phosphate in conjunction with dipyridamole have shown to be effective in the osteogenesis of critical bone defects in both skeletally immature and mature animals. Furthermore, previous studies have proven the dura and pericranium's osteogenic capacity in the presence of 3D-printed scaffolds; however, the effect galea aponeurotica on osteogenesis in the presence of 3D scaffolds remains unclear. Critical-sized (11 mm) bilateral calvarial defects were created in 35-day old rabbits (n = 7). Two different 3D scaffolds were created, with one side of the calvaria being treated with a solid nonporous cap and the other with a fully porous cap. The solid cap feature was designed with the intention of preventing communication of the galea and the ossification site, while the porous cap permitted such communication. The rabbits were euthanized 8 weeks postoperatively. Calvaria were analyzed using microcomputed tomography, 3D reconstruction, and nondecalcified histologic sectioning in order assess differences in bone growth between the two types of scaffolding. Scaffolds with the solid (nonporous) cap yielded greater percent bone volume (P = 0.012) as well as a greater percent potential bone (P = 0.001) compared with the scaffolds with a porous cap. The scaffolds with porous caps also exhibited a greater percent volume of soft tissue (P < 0.001) presence. There were no statistically significant differences detected in scaffold volume. A physical barrier preventing the interaction of the galea aponeurotica with the scaffold leads to significantly increased calvarial bone regeneration in comparison with the scaffolds allowing for this interaction. The galea's interaction also leads to more soft tissue growth hindering the in growth of bone in the porous-cap scaffolds.

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.

Effects of a biomimetic analog-based experimental bonding system on caries-affected and sound dentin.

This study compared the ultrastructure, chemical composition, and proteases activity (PA) of sound (SD) and caries-affected dentin (CAD) in the dentin hybrid layer after using an experimental bonding system containing pyromellitic dianhydride glycerol methacrylate and biomimetic analogs. The bonding system used a three step and a total-etch procedure. Polyacrylic acid (5%) and sodium trimetaphosphate (5%) were added to the primer and monocalcium phosphate monohydrate (9%), beta-tricalcium phosphate (10.5%), and calcium hydroxide (0.5%) were added to the adhesive. Transmission electron microscopy (TEM) was used to evaluate the resultant structure, particularly the adhesive-dentin and the demineralized-SD interfaces. The chemical composition was evaluated through energy-dispersive X-ray spectroscopy (EDS) and selected area electron diffraction (SAED). The PA was measured with the Coomassie Blue-G250 coloring test, and the PA data were analyzed by ANOVA. EDS identified the presence of isolated calcium phosphate nanoparticles in the demineralized region; however, the SAED analysis did not show any evidences of hydroxyapatite (HA) neoformation in SD and CAD. The biomimetic analog-based adhesive system inhibited the activities of dentin proteases immediately after treatment. Additionally, the proteolytic activity on the affected dentin resembled that of the SD. In conclusion, no HA formed in the demineralized SD and CAD although there were calcium and phosphate deposits. The experimental adhesive system inhibited dentin proteases. The present study uses a new approach to investigate the hybrid layer behavior in dentin. The experimental adhesive system was synthesized and used on sound and affected-caries dentin as the substrate to reproduce real clinical conditions.

A Multicenter, Retrospective, Case Series of Patients With Charcot Neuroarthropathy Deformities Undergoing Arthrodesis Utilizing Recombinant Human Platelet-derived Growth Factor With Beta-Tricalcium Phosphate

Charcot neuroarthropathy has traditionally been treated using both nonsurgical and surgical strategies. Recently, orthobiologics have been used to promote arthrodesis in Charcot reconstructions, obviating the need for bone graft in some cases. Recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) in combination with beta-tricalcium phosphate scaffold (β-TCP) is a bone graft substitute shown to have comparable efficacy to autograft in incidence of foot and ankle fusion. This multicenter, consecutive case series analyzed patients undergoing Charcot reconstructions utilizing rhPDGF-BB/β-TCP for joint fusion. In this cohort, 98 patients (62.24% male) with a mean age of 62.82 ± 10.28 years (range 40-87) had a fusion incidence of 217 of 223 joints (97.31%) with a mean time to fusion of 13.09 ± 4.87 weeks (range 6-30). There were 6 nonunions in the patient population. Fusion was defined as ≥50% osseous bridging based on computed tomography and/or radiographic consolidation, in addition to clinical findings. With an overall complication rate of 26.53% (26/98), adverse events occurring in more than 1 patient limb included hardware failures (n = 7, 7.14%), infection (n = 4, 4.08%), wound dehiscence (n = 4, 4.08%), amputation (n = 3, 3.06%), and death (n = 2, 2.04%). There were no adverse events related to the grafting material. From this review, we found rhPDGF-BB/β-TCP to be a safe and effective graft material that can be considered a viable alternative to autograft, even in high-risk patients such as those with Charcot neuroarthropathy.

Histomorphometric Evaluation of the Healing Process of Bony Defects Filled with Milled Teeth Versus Beta Tri-Calcium Phosphate Bone Graft Materials in Rats.

Objectives: the aim of the study was the evaluation of healing in bony defects comparing milled teeth versus beta tricalcium phosphate (B-TCP) as bone graft materials. Materials and methods: Forty-five male albino rats, were divided into three groups each group included 15 rats; one control and two experimental groups. Under general anesthesia, 1.5 cm incision was created to expose the cranial bone. Then two bone defects (each one with a diameter of 3 millimeter) were created one in each parital sides. In Group I (control group): the two bony defects (30 bony defects) were left to heal without any intervention. While, in Group II & III the bony defects were completely filled with (B-TCP) and milled teeth, respectively. At the 7th, 15th, and 30 days postoperatively five rates were randomly selected from each group to be sacrificed. Results: histomorophometric and histological results showed a higher level of bone regeneration in the two experimental groups than that of the control group all over the study period, moreover there was a significant increase in the amount of (newly formed bone) in the milled teeth than in the (B-TCP) group. The remaining particles of the two graft materials was significantly less in the milled teeth group than in the (B-TCP) group during the whole study time. Conclusion: Bone activity, formation and maturity were ahead in tooth ash filled calvarial bony defects.

Transmission Electron Microscopic Examination of the Healing Power Effect of Milled Teeth Versus Beta- Tri Calcium Phosphate Grafted in Calvarial Bone Defect in Rats.

Objectives: to evaluate the effect of milled teeth versus beta tricalcium phosphate bone graft material on new bone formation at the cell level using transmission electron microscope Materials and methods: Forty-five adult male albino rats, were divided into three main groups (n=15); control and two experimental groups. Under general anesthesia, 1.5 cm incision was done exposing the cranial bone. Then two noncritical size bone defects were created one in each parital sides of the rat calvarial bone. In Group I (control group): the bilateral calvarial bony defects were left to heal spontaneously. In Group II the bilateral calvarial bony defects completely filled with β-TCP. In Group III: the bilateral calvarial bony defects completely filled with tooth ash. Five rats from each group were sacrificed after 7, 15, and 30 days postoperatively. Results: tooth ash group: showed more new bone formation. Different types of cells appeared more active: multiple lymphocytes, fibroblast, osteoprogenitor cells, osteoblasts. Multinucleated osteoclasts with prominent vacuolated cytoplasm and ruffled border in Howship’s lacunae were clearly seen. At day 30, disappearing of the tooth ash and infiltration of different types of cells; osteoprogenitor cells, bone lining cells, and osteoblasts while β-TCP particles were still seen in the sections. Conclusion: Bone activity, formation and maturity were ahead in tooth ash filled calvarial bony defects. Tooth ash had a role in the stimulation of osteoblastic activity in matrix formation and its mineralization.

A Proof of Concept: Does Beta-tricalcium Phosphate in a Hydroxyl Sulphate Matrix Reduce Cavity Size and Problems in Revision Mastoidectomy Patients

A Proof of Concept: Does Beta-tricalcium Phosphate in a Hydroxyl Sulphate Matrix Reduce Cavity Size and Problems in Revision Mastoidectomy Patients

Load-bearing biodegradable PCL-PGA-beta TCP scaffolds for bone tissue regeneration.

A biocompatible and biodegradable scaffold with load-bearing ability is required to enhance the repair of bone defects by facilitating the attachment, and proliferation of cells, and vascularization during new bone formation. However, it is challenging to maintain the porosity and biodegradability, as well as mechanical properties (especially compressive strength), at the same time. Therefore, in the present work, a biodegradable composite structure of poly(caprolactone) (PCL) was designed using compression molding with varying amounts of poly(glycolic acid) (PGA) (25, 50, 75 wt%) and fixed amount (20 wt%) of beta tricalcium phosphate (beta TCP). It was hypothesized that the fabricated composite structure will develop porosity during the degradation of the PGA and that the corresponding decrease in mechanical properties will be compensated by new bone formation and ingrowth, in vivo. Accordingly, we have systematically studied the effects of sample composition on time-dependent dissolution and mechanical properties of the PGA/beta TCP scaffolds. The compressive strength increased up to ~92 MPa at 50% compression of the designed PCL-PGA samples. Furthermore, the dissolution rate, as well as weight loss, was observed to increase with an increase in the PGA amount in PCL. Based on the mechanical properties and dissolution data, it is concluded that the PCL-PGA scaffolds with beta TCP can be suitable candidates for bone tissue engineering applications, specifically for the reconstruction of bone defects, where strength and biodegradation are both important characteristics.

Bioactive-Enhanced Polyetheretherketone Dental Implant Materials: Mechanical Characterization and Cellular Responses.

The aim of this study was to characterize the mechanical properties of a bioactive-modified polyetheretherketone (PEEK) manufacturing approach for dental implants and to compare the in vitro biological behavior with titanium alloy (Ti6Al4V) as the reference. PEEK, PEEK with 5% hydroxyapatite (HA), PEEK with 5% beta-tricalcium phosphate (βTCP), and Ti6Al4V discs were produced using hot pressing technology to create a functionally graded material (FGM). Surface roughness values (Ra, Rz), water contact angle, shear bond strength, and Vickers hardness tests were performed. Human osteoblasts and gingival fibroblasts bioactivity was evaluated by a resazurin-based method, alkaline phosphatase activity (ALP), and confocal laser scanning microscopy (CLSM) images of fluorescent-stained fibroblasts. Morphology and cellular adhesion were confirmed using field emission gun-scanning electron microscopy (FEG-SEM). Group comparisons were tested using analysis of variance (Tukey post hoc test), α = .05. All groups presented similar roughness values (P > .05). Ti6Al4V group was found to have the highest contact angle (P < .05). Shear bond strength and Vickers hardness of different PEEK materials were similar (P > .05); however, the mean values in the Ti6Al4V group were significantly higher when compared with those of the other groups (P < .05). Cell viability and proliferation of osteoblast and fibroblast cells were higher in the PEEK group (P < .05). PEEK-βTCP showed the highest significant ALP activity over time (P < .05 at 14 days of culture). An enhanced bone and soft-tissue cell behavior on pure PEEK was obtained to the gold standard (Ti6Al4V) with equivalent roughness. The results substantiate the potential role of chemical composition rather than physical properties of materials in biological responses. The addition of 5% HA or βTCP by FGM did not enhance PEEK mechanical properties or periodontal cell behavior.

Evaluation of maxillary sinus floor augmentation with the crestal approach and beta-tricalcium phosphate: a cone-beam computed tomography 3- to 9-year follow-up

BackgroundWe performed maxillary sinus floor augmentation using the crestal approach and beta-tricalcium phosphate (β-TCP) and a long-term evaluation using cone-beam computed tomography (CBCT).MethodsTwenty-three patients (30 implants) underwent sinus floor augmentation using the osteotome technique. Subjects underwent CBCT imaging before surgery, immediately after surgery, and at follow-up (≥ 3 years after surgery). We measured the changes in height of the augmented sinus floor (SL), the augmented bone above apex of the implant (BH), and the implant length that projected into the sinus (IL).ResultsThe mean SL decreased from 6.54 ± 1.51 (immediately after surgery) to 3.11 ± 1.35 mm (follow-up). The mean BH decreased from 3.17 ± 0.97 to − 0.25 ± 1.19 mm; the maxillary sinus floor in many implants was near the apex at follow-up. The SL at follow-up showed a strong correlation with the IL (p = 0.0057).ConclusionsOsteotome sinus floor elevation with beta-tricalcium phosphate was clinically effective. Cone-beam computed tomography analysis revealed that ≥ 3 years after surgery, the maxillary sinus floor was near the apex of the implant.

In vitro and in vivo evaluation of the pH-neutral bioactive glass as high performance bone grafts.

Osteogenic and angiogenic properties are two most valued factors for bone grafting materials. Biomedical materials with synergistic promotion effects on these two properties would be highly desirable. In this study, we showed that a recently developed pH-neutral bioactive glass (PSC) possessed such characteristics. Compared to two classical biomaterials, 45S5 bioactive glass and beta-tricalcium phosphate (β-TCP), PSC markedly improved BMSCs' proliferation, migration and mineralization as well as their osteogenic and angiogenic differentiation. In vivo, PSC showed better performance on inducing bone regeneration than both 45S5 and β-TCP, as featured by elevated bone mineral density (BMD) and new bone areas. PSC also significantly promoted new blood vessels formation compared with those in control groups. Furthermore, we revealed that PSC induced osteogenic and angiogenic differentiation of BMSCs through the PI3K/Akt/HIF-1α pathway, which had not been reported before. This synergistic effect of the PI3K/Akt/HIF-1α pathway on osteogenesis and angiogenic differentiation of BMSCs suggested that biomedical materials may promote new bone formation through multiple signal pathways, thus shedding light on the future development of materials with better performance.

A 3D-printed, personalized, biomechanics-specific beta-tricalcium phosphate bioceramic rod system: personalized treatment strategy for patients with femoral shaft non-union based on finite element analysis

BackgroundAlthough double-plate fixation (DP), i.e., fixation with a combination of a main lateral plate (LP) and a support medial plate (MP), is a relatively mature method for treating femoral shaft non-union with bone defect causes complications. The purpose of this study was to evaluate LP fixation with a 3D-printed, personalized, biomechanics-specific β-TCP bioceramic rod system (LP + 3DpbsBRS) as an alternative with less collateral damage.MethodsStructure-specific finite element modelling was used to simulate femoral shaft non-union with bone defects and treatment with an LP only as the blank control. Then, the peak von Mises stress (VMS), the VMS distribution, and the plate displacement were determined to compare the effectiveness of LP + CBG (cancellous bone grafting), DP + CBG, and LP + 3DpbsBRS under 850 N of axial force.ResultsOur results indicated that the peak VMS was 260.2 MPa (LP + 3DpbsBRS), 249.6 MPa (MP in DP + CBG), 249.3 MPa (LP in DP + CBG), and 502.4 MPa (LP + CBG). The bending angle of the plate was 1.2° versus 1.0° versus 1.1° versus 2.3° (LP + 3DpbsBRS versus MP in DP + CBG versus LP in DP + CBG versus LP + CBG).ConclusionThe 3DpbsBRS in the LP + 3DpbsBRS group could replace the MP in the DP + CBG group by providing similar medial mechanical support. Furthermore, avoiding the use of an MP provides better protection of the soft tissue and vasculature.

Bioinspired scaffolds with hierarchical structures for tailored mechanical behaviour and cell migration

Replacement and regeneration of damaged bone, particularly for those defects with critical size, are still major challenges in orthopaedic surgery. The conventional bone implants, normally with poor internal architecture design, may cause significant issues owing to the mechanical and structural mismatches between target bone and the implants. In this work, as inspired by hierarchical natural bone, for the first time, we developed hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) scaffolds with three-level hierarchical structures across macro to nano scale using combined 3D printing (3DP) and freeze casting routines. It is clear these hierarchical porous scaffolds significantly enhance cell penetration (over 7 times) while maintaining cell proliferation ability. With three levels of hierarchies, the overall mechanical behaviour of the scaffolds can be tailored to be comparable to general cancellous bone (ranging from 1 to 6 MPa), demonstrating great potential for practical applications. Additionally, the combination of nanoindentation and mechanics model makes it possible to predict the mechanical behaviour of scaffolds at micro and macro scales.

PECULIARITIES OF REVASCULARIZATION (OR ANGIOGENESIS) OF THE ALVEOLAR AGES USING DIFFERENT BONE-PLASTIC MATERIALS

Secondary anodontia, as a consequence of diseases of the dentoalveolar apparatus is the most common pathology among the population. The results of medical and statistical studies show an increase in the incidence of acquired anodontia in both adults and children.&#x0D; When teeth are lost, bone resorption occurs and this leads to a decrease in the thickness and height of the alveolar processes of the jaws by an average of 25-30%. In addition, there is a loss of bone walls of the dental alveolus, which causes a tissue defect. To eliminate defects and deformations of the walls of the alveolar processes of the jaws, the method of osteosynthesis of autografts in the form of a block of the bone of appropriate volume or controlled bone growth is used.&#x0D; Angiogenesis and blood supply to the cavitary defects of the jaw bones is one of the important indicators of bone graft integration and restoration of the authentic structure of bone tissue at the defect site.&#x0D; However, blood supply recovery depending on the type of graft has not yet been fully elucidated, which is why the study of angiogenesis in limited defects after their replacement by different types of grafts remains relevant.&#x0D; The aim of the research is to study of the features of revascularization of bone regenerates depending on the type of osteoplastic material used.&#x0D; Material and methods of experimental research&#x0D; Experimental studies were performed on 50 male Wistar rats weighing 270-380 g in the vivarium of the State Research Control Institute of Veterinary Drugs and Feed Additives (Lviv).&#x0D; The experimental animals were divided into 5 experimental groups.&#x0D; In groups 2 and 3, we used xenogenic bone-plastic materials:&#x0D; group 1 - healing took place under a blood clot (10 animals);&#x0D; group 2 - Bio-Oss® (Switzerland), a bone mineral of natural origin derived from bovine bone (10 animals);&#x0D; group 3 - Osteoplast-K (Russia), highly purified non-demineralized bone collagen isolated from cancellous bone, which contains sulfated glycosaminoglycans. (10 animals);&#x0D; In groups 4 and 5, we used bone-plastic materials based on calcium phosphate:&#x0D; group 4 - Easy-Graft) (Switzerland), material based on beta-tricalcium phosphate (10 animals);&#x0D; group 5 - Collapan-L (Russia), biocomposite material based on synthetic hydroxyapatite, collagen and antibiotic (lincomycin hydrochloride) (10 animals).&#x0D; The method of bone defect formation in experimental conditions. Under ether anesthesia in aseptic conditions after depilation of the operating field, we made an incision in the dorsal surface of the tibia, created access to the bone surface and formed two defects with a spherical boron (one on each side) according to the topographic and anatomical features of the tibia structure of experimental animals.&#x0D; The formed bone defect on one side was filled with osteoplastic material; on the opposite side, healing took place under a blood clot.&#x0D; It was found that when using osteoplastic materials Bio-Oss® and Osteoplast-K, the most active formation of blood vessels occurred from the 30th to the 60th day of the experiment (from 79.13 ± 2.67% to 81.83 ± 3.68% of vessels caliber 0-20 μm). When using materials Easy-Graft ™ and Collapan-L, the most active formation of vessels was observed from the 60th to the 90th day (from 45.24 ± 3.84% to 90.63 ± 1.63% of vessels of caliber 0-20 μm2). In the control group, where healing took place under a blood clot, the most active vascular formation was observed up to the 14th day (84.28 ± 1.36% of vessels of caliber 0-20 μm2) and up to the 60th day (82.01 ± 1.95%).

Promoting Osseointegration of Dental Implants in Dog Maxillary Sinus Floor Augmentation Using Dentin Matrix Protein 1-Transduced Bone Marrow Stem Cells.

Beta-tricalcium phosphate (β-TCP) has been employed successfully as a synthetic graft material in maxillary sinus floor augmentation (MSFA) for placing dental implants. However, the lack of osteogenic and osteoinductive properties of this substitute invariably results in bone regeneration of low quality and quantity. The purpose of this study was to determine whether loading dentin matrix protein-1 (DMP1) gene-modified bone marrow mesenchymal stem cells (BMSCs) onto β-TCP promoted bone regeneration and osteointegration of dental implants in MSFA of dogs. BMSCs were transduced with a lentiviral vector overexpressing the DMP1 gene (Lenti-DMP1) and with a lentiviral vector overexpressing enhanced green fluorescent protein (Lenti-EGFP) in vitro and were loaded into β-TCP scaffolds for autologous sinus grafting. Beagles received bilateral MSFA with four biomaterials (① Lenti-DMP1-transduced BMSCs/β-TCP, ② Lenti-EGFP-transduced BMSCs/β-TCP, ③ BMSCs/β-TCP, ④ β-TCP) and simultaneous implant placement at each sinus. Twelve weeks post operation, the maxillae were explanted, and every sinus was evaluated by radiographic observation, micro-CT and histological analysis. The osteogenic outcomes of bone regeneration and osseointegration were compared between the four groups. The sinuses grafted with Lenti-DMP1-transduced BMSCs/β-TCP constructs presented a significantly higher increase in compact radiopaque area, higher local bone mineral densities, greater bone-implant contact and greater bone density when compared to other three groups. These results demonstrated that combinations of β-TCP and DMP1 gene-modified BMSCs could be used to construct tissue-engineered bone to enhance mineralization of the regenerated bone and osseointegration of dental implants in MSFA.

Jaw Periosteal Cells Seeded in Beta-Tricalcium Phosphate Inhibit Dendritic Cell Maturation.

Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating and regulating immune reactions by promoting antigen-specific T cell activation. In this study, we investigated the effect of human jaw periosteal progenitor cells (JPCs) seeded in beta-tricalcium phosphate (β-TCP) scaffolds on monocyte-derived DC differentiation. Significantly lower numbers of differentiated DCs were observed in the presence of normal (Co) and osteogenically induced (Ob) JPCs-seeded β-TCP constructs. Gene expression analysis revealed significantly lower interleukin-12 subunit p35 (IL-12p35) and interleukin-12 receptor beta 2 (IL-12Rβ2) and pro-inflammatory cytokine interferon-gamma (IFN-γ) levels in DCs under Ob conditions, while interleukin-8 (IL-8) gene levels were significantly increased. Furthermore, in the presence of JPCs-seeded β-TCP constructs, interleukin-10 (IL-10) gene expression was significantly induced in DCs, particularly under Ob conditions. Analysis of DC protein levels shows that granulocyte-colony stimulating factor (G-CSF) was significantly upregulated in coculture groups. Our results indicate that undifferentiated and osteogenically induced JPCs-seeded β-TCP constructs have an overall inhibitory effect on monocyte-derived DC maturation.

Injectable bone substitute based on chitosan with polyethylene glycol polymeric solution and biphasic calcium phosphate microspheres

We described a method to produce an injectable bone substitute consisting of a solid and liquid phase, this solid was formed using the coacervation method consisting of a mixture of Hydroxyapatite (HAp) and beta-Tricalcium Phosphate (β-TCP) which the sodium alginate - precursor - was removed during sinterization. The biphasic calcium phosphate microspheres had varying size distributions depending on the flow rate and these microspheres were mixed with a polymeric solution, chitosan and polyethylene glycol, and depending on the ratio of these phases, the injectability results varied. Nonetheless, the force required for complete removal will not disrupt the accuracy of injection into the bone defect while the biomaterial exhibited no cytotoxicity with promising results from in vivo using tibia bone defect in rabbits at 30 and 60 days whereas bone repair was more intense and accentuated with the usage of the biomaterial, and was gradually absorbed during the evaluated periods.

Biomaterials preparation by electrospinning of gelatin and sodium hyaluronate/gelatin nanofibers with non-toxic solvents

Gelatin (Ge) based fibers have been produced by electrospinning with a non-toxic solvent for preparing membranes usable in maxillofacial surgery. Ge and Ge/sodium hyaluronate (SH) nanofibers were successfully electrospun to produce membranes whose thickness was around 150 to 200μm. The mean fiber diameter reached a maximum of 660nm for Ge fibers and 210nm for Ge/SH fibers. The presence of Ge and SH was confirmed in the membranes by Raman spectroscopy. Ge membranes had low mechanical properties and only small samples of 0.5cm in size could be retrieved from the collector as larger sample tended to tear and break. Ge/SH membranes could be retrieved from the collector slightly easily. Membranes could be handled carefully but in vivo implantation could not be planned due to poor mechanical resistance. Crosslinking by glutaraldehyde vapors reduced the mean porosity of Ge membranes; it totally prevents membranes to be retrieved from the collector. Beta tricalcium phosphate (β-TCP) particles were added with Ge during electrospinning to increase osseointegration of the membranes and promote bone formation. β-TCP particles formed agglomerates outside the fibers, and we could not obtain β-TCP particles inside the Ge fibers due to their low diameter. In general, electrospun membranes lacked reproducibility. Despite the great interest of Ge-based membranes and Ge/β-TCP membranes, the low mechanical properties of the fibers, the lack of reproducibility and the difficulty to retrieve the membranes from the collector did not allow our biomaterials to be implanted or to be envisaged for industrial production.